Chromosomal breakage correlates with delayed lethality in normal and ataxia telangiectasia cell lines treated with bleomycin

Abstract

Cytogenetic damage and cytotoxicity produced by a range of acute treatments with bleomycin (BLM) were investigated in three B-lymphoblastoid cell lines: EM-OC, PA-AT and CP-NC: established from heterozygous, and homozygous, ataxia telangiectasia (AT) and normal donors, respectively. The following endpoints were studied: (1) the maximum (initial) yields of different classes of chromosomal aberrations (CA) produced in G 2-phase; (2) the percentage distributions of cells within bins with different numbers of CA; (3) short-term (0–48 h) viability and proliferation; and (4) (delayed) lethality, as measured by a modified limiting-dilution assay. While only slight losses of short-term viability and proliferation were detectable after standard BLM pulse-treatment at 25 or 100 μg/ml (results for latter dose given in parentheses), both regimes subsequently led to intense lethality as follows: CP-NC, 79.3% (95.1%); EM-OC, 90.4% (96.7%) and PA-AT, 98.4% (99.9%). Relative lethality after the respective BLM treatments increased 6.2 × (48.3 × ) among PA-AT cells more than in controls —resembling the corresponding ratios for chromosome breaks (csb) of 7.0 × (30.9 × ), more than those for chromatid breaks (ctb) of 3.1 × (2.7 × ). EM-OC exhibited slightly increased relative lethality after the respective BLM treatments at 2.15 × (1.45), and increased aberration sensitivities for csb of 3.0 × (14.0), while the corresponding ratios for ctb were actually lower at 0.66 × (0.50 × ). Significant correlations were observed between lethality and both, the yields of most types of chromosomal aberrations (excepting unambiguous exchanges) and also, the percentages of cells bearing CA.